Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242379 (lung cancer)
 71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patients with extensive small-cell lung cancer were given induction chemotherapy consisting of cyclophosphamide, vincristine, cisplatin, and etoposide (COPE) every 3 weeks for four cycles. Responding patients then received chest and elective whole-brain irradiation. Patients presenting with brain metastases received therapeutic brain irradiation during the first cycle of chemotherapy. No maintenance therapy was given, but two late intensification cycles of COPE were given at weeks 24 and 48. Among the 34 evaluable patients, the response rate to induction chemotherapy was 59%, with 10% achieving a complete response (CR) and 49%, a partial response (PR). Of the 18 patients who completed chest irradiation, 3 achieved a CR, producing an overall CR rate of 18%. Five patients completed the projected course of treatment. The median duration of response for all patients was 8 months (range, 2-30+ months) and the median survival was 9 months (range, 1-30+ months). Complete responders had a median response duration of 9 months and a median survival of 11 months. This regimen produced significant myelosuppression, with 5 neutropenic deaths (13%) occurring in the 38 patients evaluable for toxicity; an additional 16% required hospitalization for fever while neutropenic. Only six patients (13%) had nadir platelet counts of less than 50,000/mm3 with no episodes of thrombocytopenic hemorrhage. Nausea, vomiting, and neurotoxicity were mild to moderate in all patients. One patient with no evidence of disease died of radiation pneumonitis at 6 months. While producing significant toxicity, this regimen did not result in a CR rate or survival advantage that would suggest its superiority over standard regimens for small-cell lung cancer.
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PMID:Cyclophosphamide, vincristine, cisplatin, VP-16 and radiation therapy in extensive small-cell lung cancer. A Southwest Oncology Group Study. 254 13

Control of cisplatin-induced nephrotoxicity and nausea/vomiting has enabled the development of very high-dose cisplatin regimens (monthly total dose, 200 mg/m2). Neurotoxicity is now recognized to be the dose-limiting toxicity of these regimens. However, during a pilot study involving 5 mg/m2 vinblastine and 100 mg/m2 cisplatin given every 28 days on days 1 and 8 for the treatment of advanced non-small-cell lung cancer, we noted a high incidence of progressive peripheral neuropathy, which continued for several months after the discontinuation of cisplatin chemotherapy. Of the six patients treated, four received at least three cycles of therapy (median total cisplatin dose, 685 mg/m2; range, 500-725 mg/m2). All four patients developed a progressive peripheral neuropathy, with a worsening of toxicity by 1-3 grades over the 2-3 months after cisplatin discontinuation. One patient progressed from grade I (mild paresthesia) to grade IV (inability to ambulate) over a period of 3 months after the discontinuation of therapy. Stricter rules for early dose de-escalation and discontinuation may be required for very high-dose cisplatin regimens. Delayed progressive neuropathy should be recognized as a possible late complication of this form of therapy.
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PMID:Progressive paresthesias after cessation of therapy with very high-dose cisplatin. 255 19

The efficacy and toxicity of carboplatin 100 mg/m2, administered intravenously (IV) daily X 3, and VP-16-213 120 mg/m2, IV daily X 3, administered every 28 days for six courses, was assessed in 94 (36 limited stage, 58 extensive stage) previously untreated patients with small-cell lung cancer. Mediastinal irradiation using 50 Gy in 25 fractions was given to all limited-stage patients with a complete (CR) or partial response (PR) after three chemotherapy courses. Cranial irradiation was administered to all patients with CR. Objective responses were seen in 77% (CR 40%, PR 37%) of patients with limited-stage and 58% (CR, 9%; PR, 49%) with extensive-stage disease. Median relapse-free survival for objective responders with limited stage was 14.6 months and 7.9 months for extensive-stage patients. Median relapse-free survival following CR was 15.4 months and 8.5 months for PR. Median survival was 15.3 months for limited-stage and 8.1 months for extensive-stage patients. The combination was well tolerated with mild nausea or less (World Health Organization [WHO] grade 0 or 1) in 62% of patients and minimal mucositis, renal, neurotoxicity, or ototoxicity. Neutropenia less than 1.0 X 10(9)/L (WHO grade 3 or 4) was seen in 63% of patients, with two deaths from infection while neutropenic. The combination of carboplatin and VP-16-213 is a new, active program with low toxicity when applied intensively in previously untreated patients with small-cell lung cancer.
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PMID:Carboplatin (CBDCA, JM-8) and VP-16-213 in previously untreated patients with small-cell lung cancer. 282 Nov 97

A total of 144 patients with small-cell lung cancer (SCLC) were randomized to receive cisplatin/etoposide (PE) or ifosfamide/etoposide (IE) combination chemotherapy. PE consisted of cisplatin, 80 mg/m2, intravenously (IV) on day 1, and etoposide, 150 mg/m2, IV on days 3 through 5. IE consisted of ifosfamide, 1,500 mg/m2, IV on days 1 through 5, and etoposide, 120 mg/m2, IV on days 3 through 5. Six cycles were administered in 3-week intervals. Nonresponders were switched immediately to CAV, consisting of cyclophosphamide, 600 mg/m2, IV on days 1 and 2, Adriamycin (Adria Laboratories, Columbus, OH), 50 mg/m2, IV on day 1, and vincristine, 2 mg, IV on day 1. Patients obtaining complete remission (CR) received prophylactic cranial irradiation with 30 Gy. After completion of chemotherapy, patients with limited disease received chest irradiation with 45 Gy. No maintenance therapy was given to patients in CR. Minimum follow-up was 2 years. Of the 141 patients evaluable, the overall response rate was 65% in PE therapy and 68% in IE therapy. The CR rate was 32% v 20% for all patients, 50% v 24% for limited disease, and 22% v 18% for extensive disease, all in favor of PE therapy. Median survival for all patients was 11.6 months v 9.4 months, for limited disease 14.8 months v 11.0 months, and for extensive disease 8.9 months v 7.5 months, all preferring PE therapy. The 2-year survival rate was higher in PE therapy than in IE therapy for all patients (12% v 9%) and for limited disease (23% v 10%), but not for extensive disease (5% v 9%). Median progression-free survival was 7.5 months v 6.0 months for all patients, 12.2 months v 8.8 months for limited disease, and 5.9 months v 4.4 months for extensive disease, all in favor of PE. Relapse in the area of the primary tumor was found less often after PE than after IE therapy (25% v 38%). Response to second-line CAV was seen in 30% of patients with prior PE and 43% with prior IE therapy, but was usually short lasting, and only one patient achieved CR. Toxicity included three lethal complications. Nausea, vomiting, diarrhea, and skin lesions occurred more often after PE than after IE therapy. These results suggest that PE is superior to IE chemotherapy in limited-stage, but not in extensive-stage SCLC, and that CAV is cross-resistant to PE, as well as to IE in the majority of patients.
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PMID:Cisplatin/etoposide versus ifosfamide/etoposide combination chemotherapy in small-cell lung cancer: a multicenter German randomized trial. 282 10

A previously healthy 50-year old man presented with acute small bowel obstruction. No etiology was found at laparotomy. Postoperatively, the patient remained symptomatic with nausea, vomiting and severe constipation. Gastroscopy revealed retained food in the stomach. Gastric emptying of solids and liquids was dramatically decreased at scintigraphy. The colon was dilated on X-ray study. Chest X-ray revealed a pneumopathy and a small-cell lung cancer was discovered at bronchoscopy. The patient died 5 months after onset. Histologic study of the gut showed widespread degeneration of the myenteric plexus with plasma cell infiltration, Schwann cell proliferation and a reduced number of neurons of which many were abnormal. Intestinal pseudo-obstruction can reveal a small-cell lung cancer; the mechanism of neuronal impairment leading to pseudo-obstruction remains unknown, but could be related to the pathophysiology of paraneoplastic syndromes.
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PMID:Paraneoplastic intestinal pseudo-obstruction as the presenting feature of small-cell lung cancer. 283 68

Forty-two patients with advanced lung cancer undergoing chemotherapy containing cisplatin (80 mg/m2) were submitted to a randomized controlled trial to evaluate the effect of the combination of metoclopramide and dexamethasone for the treatment of delayed cisplatin-induced emesis occurring more than 24 hours after cisplatin administration. All patients received intravenously (i.v.) high-dose metoclopramide and dexamethasone on the day of cisplatin treatment. Excellent emetic control (no emesis during the 24 hours following cisplatin administration) was achieved in 30 out of 41 patients (73%) with this combination. Patients treated i.v. with metoclopramide and dexamethasone on days 2-7 experienced less delayed emesis, nausea and anorexia compared to those treated with a placebo (delayed emesis, 25 vs 50%, respectively, P = 0.105; more than four days of nausea, 10 vs 35%, respectively, P = 0.059; less than three days of anorexia, 80 vs 50%, respectively, P = 0.048). Although the results of the study showed no statistically significant advantage with the combination of i.v. metoclopramide and dexamethasone for patients treated with cisplatin, in view of the short duration of anorexia and the marginal reduction in nausea. Female patients tended to have more emetic episodes and extrapyramidal side effects (except akathisia) than male patients, but the differences were not statistically significant except for acute emesis (P less than 0.005).
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PMID:Control of cisplatin-induced delayed emesis with metoclopramide and dexamethasone: a randomized controlled trial. 292 17

A phase II study of VP-16, a semisynthetic Podophyllotoxin, was performed in patients with solid tumors. VP-16 was administered orally at a dose of 200mg/day for 5 consecutive days at 3 to 4-week intervals. Out of 41 patients who were entered into the study, 35 patients comprising 17 lung cancer, 10 hepatoma and 8 other tumors were evaluable. There were 4 partial responses (23.5%) for lung cancer, 1 (10.0%) for hepatoma and 1 for rhabdomyosarcoma. Overall response rate was 18.2% for patients with prior chemotherapy and 15.4% for those given no prior chemotherapy respectively. Thus the results indicated VP-16 has no cross-resistance to other antitumor agents. Leukopenia (less than 4,000/mm3) and thrombocytopenia (less than 10 X 10(4)/mm3) were observed in 72.7% and 29.4% of the patients, respectively. Other toxicities were alopecia (59.5%) and gastrointestinal disturbances such as nausea (46.2%), vomiting (20.5%) and anorexia (20.5%), but these were all well tolerated.
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PMID:[Phase II study of VP-16 (capsule) in solid tumors. A cooperative study]. 298 32

A clinical trial of a new semi-synthetic podophyllotoxin, VP-16, was undertaken in patients with primary lung cancer; 56 of the 81 evaluable patients had small cell carcinoma, 9 adenocarcinoma, 8 epidermoid carcinoma, 7 large cell carcinoma, and 1 adenosquamous carcinoma. A dose of 200 mg/body/day orally for 5 consecutive days was administered every 3 to 4 weeks. Partial response (PR) was attained in 19 out of 81 (23%) and PR + MR was 35 out of 81 (43%). PR and minor response (MR) were seen as follows; small cell carcinoma, 17 PR (30%), 13 MR; epidermoid carcinoma, 2 PR (25%), 1 MR; adenocarcinoma, 1 MR; adenosquamous carcinoma, 1 MR. The dose-limiting factor was leukopenia, while thrombocytopenia was experienced in 2 cases. Clinical toxicities noted were anorexia, nausea, vomiting, stomatitis, diarrhea and alopecia, but these were well tolerated in all cases. The result indicated that VP-16 has considerable efficacy in small cell carcinoma and epidermoid carcinoma of the lung and hence its usefulness in combination chemotherapy was suggested.
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PMID:[A phase II study of oral VP-16 in primary lung cancer]. 299 76

Epirubicin (4'-epidoxorubicin) is an antineoplastic agent derived from doxorubicin. The compounds differ in the configuration of the hydroxyl group at the 4' position. Epirubicin, like doxorubicin, exerts its antitumor effects by interference with the synthesis and function of DNA and is most active during the S phase of the cell cycle. Epirubicin is administered by intravenous (IV) injection. It is metabolized by the liver and primarily eliminated in the bile. About 10% of the drug is eliminated in the urine. Dosage adjustments are recommended for patients with liver metastases or elevated liver function tests. The elimination half-life of epirubicin is 30 to 40 hours. Clinical studies indicate activity in breast cancer, non-Hodgkin's lymphomas, ovarian cancer, soft-tissue sarcomas, and pancreatic cancer. There is also evidence of activity against gastric cancer, small-cell lung cancer, and acute leukemia. Epirubicin has limited activity as a single agent against head and neck tumors or non-small-cell lung cancer, but may be beneficial in combination with other agents. The overall activity of epirubicin appears to be comparable with that of doxorubicin. However, more studies are needed to define its role in combination chemotherapeutic regimens. The acute dose-limiting toxicity of epirubicin is myelosuppression. Nausea, vomiting, and alopecia are also common. Epirubicin may cause transient cardiac arrhythmias and alterations of the electrocardiogram. Chronic therapy is limited, but available data indicate that epirubicin can be administered in higher cumulative doses than doxorubicin before cardiotoxicity limits further therapy.
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PMID:Epirubicin: a review of the pharmacology, clinical activity, and adverse effects of an adriamycin analogue. 300 21

Sixty patients with inoperable non-small-cell lung cancer (NSCLC) were entered into a phase II study that tested the combination of cisplatin (80 mg/m2, day, etoposide intravenously (IV) (100 mg, days 1 and etoposide orally (200 mg/m2, days 3 and 5). The regimen was repeated every 28 days for six courses, after which patients were allowed to receive additional treatment at the discretion of their physician. Overall objective response rate in 51 evaluable patients was 69% (95% confidence interval: range, 56% to 81%), with 16% sustaining complete remission (CR), 53% partial remission (PR), 17% stable disease (SD), and 14% progressive disease (PD). CR was pathologically confirmed by bronchoscopy and biopsy. One patient with a clinical PR underwent surgery and was shown to have a pathologic CR. Median survival of all evaluable patients was 52 weeks, greater than 75 weeks for CR patients, 52 weeks for PR patients, 42 weeks for SD patients, and 13 weeks for PD patients. Eleven patients (21.5%) developed CNS metastases, which resulted in the deaths of ten. Survival was significantly correlated with extent of disease, performance status, and albumin level, but not with histology or weight loss. Tumor response was significantly correlated only with histology (squamous-cell and large-cell undifferentiated carcinoma greater than adenocarcinoma). Side effects were nausea, vomiting, anorexia, alopecia, bone marrow suppression, and nephrotoxicity. One patient died from leukopenia and sepsis. Pharmacokinetic studies in ten patients showed the continuous presence of etoposide in plasma for six days at a level of at least 220 to 480 ng/mL. In order to investigate whether this very effective combination of cisplatin and etoposide can prolong survival in NSCLC, it will be tested as preoperative chemotherapy in a randomized trial in operable patients with T1N1 and T2N0-1 disease.
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PMID:A multicenter phase II trial of cisplatin and oral etoposide (VP-16) in inoperable non-small-cell lung cancer. 302 Jul 7


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